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Telomerase Activity in Human Stem Cells
Overview Telomerase is the ribonucleoprotein that regulates the addition of telomeres - the areas at the end of each chromosome that add a sequence of nonsense repeats to the DNA sequence to provide a “cushion” for the coding portion of the DNA strand that ensures none of the necessary code is clipped off during replication. Telomerase is present primarily in stem cells, where high levels of this enzyme are present to ensure the organism’s gametes (as well as a select few additional cells, such as bone marrow) continuously replicate to prevent the organism’s offspring from accumulating mutations as a result of cellular aging or replication within the gametes. Telomerase activity is also high in cancer cells. The correlation between the two is investigated by various studies and show that there is a strong indication that cancer cells and telomerase activity is linked. Mechanics and Control Telomerase acts within stem cells to allow for their infinite replication. In other areas of the body, such as somatic cells, telomerase activity declines after infancy and continues to do so throughout the individual’s life – this causes cellular senescence. In this way, telomerase activity is controlled to allow an organism’s gametes (as well as a select few additional cells, such as bone marrow) to continuously replicate to ensure that the organism’s offspring will not have accumulated mutations as a result of cellular aging or replication within the gametes. The exception to this otherwise conclusive rule is cancer. Cancerous cells are no longer able to control their rate of replication and therefore divide non-stop, causing a malignant disease. Telomerase Activity in Cancer Cancer cells are unlike other somatic cells of the body in the sense that they behave more like gametes in their ability to divide; however, unlike gametes, this division is uncontrolled by the cellular checkpoints and apoptosis present in normal somatic cells and gametes. Furthermore, this uncontrolled cellular division and differentiation is malignant, harming the individual as more affected cells are produced. On top of this, these cancerous cells may spread to other parts of the body through the blood stream in the process of metastasis. Different studies suggest various things about the nature of telomerase activity in human somatic cells. For example, one study suggests that the methodical suppression of telomerase activity in somatic cells indicates that the malignant progression of cancerous cells may depend on the activation of telomerase, and that species that live long lives, such as humans, developed the suppression of telomerase in older cells to prevent the likelihood of developing cancerous cells with uncontrolled telomerase activity (Kim 1994). A separate study found that the Wnt/β-signaling pathway, which controls various processes during embryonic development and is very active in both embryonic and adult stem cells, possesses a molecular link to telomerase (Hoffmeyer 2012). This pathway is heavily reliant on the β-catenin protein, which if regulated incorrectly or mutated, produces tumors. β-catenin has been shown to directly regulate the telomerase gene, and explains its molecular mechanism. The scientists working on the project found that embryonic stem cells which had mutated β-catenin had larger telomeres and generated more telomerase, while the opposite was true for those lacking the β-catenin. Additionally, it was discovered that this same regulation mechanism is present in human cancer cells. (Hoffmeyer 2012). This provides a strong indication that this signaling pathway and the mutation of its β-catenin protein may directly influence the production of cancerous cells from embryonic stem cells. These tables illustrate the telomerase activity present in both normal somatic cells and cancerous cells throughout the human body, allowing the correlation between the two to be seen (Kim 1994). Research, Potential, & Ethical Concerns Stem cells are a unique area of study relating to the human body due to their numerous potential uses – not only in research, but also in the manufacturing of treatments for diseases. Though telomerase appears to be a crucial element in stem cell reproduction and renewal, much is still unknown about this enzyme due to obstacles set in the path of this branch of research due to laws of various degrees world-wide. Due to the origin of stem cells, many individuals believe that humans should not be tampering with “potential offspring” or should not try to “play God”. Unfortunately, this manner of thinking, among others, hinders the growth of our knowledge relating to stem cells and their potential benefits. Currently, it is still unknown how undifferentiated stem cells become differentiated stem cells which then proceed to function normally in the body, allowing us to go about our lives uninterrupted by the daily loss of cells via apoptosis by replenishing our old cells with fresh, new cells. What is currently known about this process has to do with cells being controlled by gene expression and regulation, which affects every aspect of our body. However, as previously discussed, some of these new cells possess one or more mutations which make them cancerous and thus unable to control their cell division and differentiation (Stem Cell Basics 2002). Since stem cell research would provide insight in the division of these pluripotent cells, they may provide insight into both normal undifferentiated cell division and into the uncontrolled cell division seen in cancerous cells (Marión 2010). This research may also determine why telomerase activity is re-initiated in somatic cells that have become cancerous; by observing stem cells which naturally possess a large amount of telomerase, we may be able to determine what makes cancerous somatic cells suddenly possess high amounts of telomerase – thereby causing the disease (Geron). References Marión RM, Blasco MA. (2010). Telomeres and telomerase in adult stem cells and pluripotent embryonic stem cells. Adv Exp Med Biol. Pub Med. Internet. 11/27/2014 695:118–131. http://www.ncbi.nlm.nih.gov/pubmed/21222203 Hiyama E, Hiyama K. (2007). Telomere and telomerase in stem cells. British Journal of Cancer. Internet. 11/27/2014 96: 1020-1024 http://www.nature.com/bjc/journal/v96/n7/full/6603671a.html Hoffmeyer K, Raggioli A, Rudloff S, Anton R, Hierholzer A, Del Valle I, Hein K, Vogt R, Kemler R. (2012). Wnt/ -Catenin Signaling Regulates Telomerase in Stem Cells and Cancer Cells. Science. Internet. 11/27/2014 336 (6088): 1549 http://www.sciencemag.org/content/336/6088/1549 Kim NW, Piatyszek MA, Prowse KR, and others. (1994). Specific association of human telomerase activity with immortal cells and cancer. Science. Internet. 1994; 11/28/2014 266 (5193): 2011-2015. http://www.sciencemag.org/content/266/5193/2011.full.pdf Stem Cell Basics: Introduction. In Stem Cell Information (2002). Internet. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services. 11/27/14. http://stemcells.nih.gov/info/basics/pages/basics1.aspx Geron. Innovative Approaches: Telomerase. Geron: Telomerase. Internet. 11/27/2014 .